Alterations of Central Liver Metabolism of Pediatric Patients with Non-Alcoholic Fatty Liver Disease

Berndt, Nikolaus; Hudert, Christian; Eckstein, Johannes; Loddenkemper, Christoph; Henning, Stephan; Bufler, Philip; Meierhofer, David; Sack, Ingolf; Wiegand, Susanna; Wallach, Iwona; Holzhütter, Hermann‐Georg

doi:10.3390/ijms231911072

Cited by 6 publications

(4 citation statements)

References 47 publications

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“…Although all the rabbits were genetically identical and received the same nutrition, there were clear differences in fatty-acid metabolism, ketone-body synthesis and urea metabolism. While this is the first time we studied rabbit liver, variability in metabolic capacities were also shown in healthy mouse liver as well as human pediatric patients with moderate liver fibrosis ( Berndt et al, 2021b ; Berndt et al, 2022 ).…”

Section: Discussionmentioning

confidence: 95%

On the relationship between metabolic capacities and in vivo viscoelastic properties of the liver

Shahryari

Keller

Meierhofer

et al. 2023

Front. Bioeng. Biotechnol.

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The liver is the central metabolic organ. It constantly adapts its metabolic capacity to current physiological requirements. However, the relationship between tissue structure and hepatic function is incompletely understood; this results in a lack of diagnostic markers in medical imaging that can provide information about the liver’s metabolic capacity. Therefore, using normal rabbit livers, we combined magnetic resonance elastography (MRE) with proteomics-based kinetic modeling of central liver metabolism to investigate the potential role of MRE for predicting the liver’s metabolic function in vivo. Nineteen New Zealand white rabbits were investigated by multifrequency MRE and positron emission tomography (PET). This yielded maps of shear wave speed (SWS), penetration rate (PR) and standardized uptake value (SUV). Proteomic analysis was performed after the scans. Hepatic metabolic functions were assessed on the basis of the HEPATOKIN1 model in combination with a model of hepatic lipid-droplet metabolism using liquid chromatography–mass spectrometry. Our results showed marked differences between individual livers in both metabolic functions and stiffness properties, though not in SUV. When livers were divided into ‘stiff’ and ‘soft’ subgroups (cutoff SWS = 1.6 m/s), stiff livers showed a lower capacity for triacylglycerol storage, while at the same time showing an increased capacity for gluconeogenesis and cholesterol synthesis. Furthermore, SWS was correlated with gluconeogenesis and PR with urea production and glutamine exchange. In conclusion, our study indicates a close relationship between the viscoelastic properties of the liver and metabolic function. This could be used in future studies to predict non-invasively the functional reserve capacity of the liver in patients.

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Section: Discussionmentioning

confidence: 95%

On the relationship between metabolic capacities and in vivo viscoelastic properties of the liver

Shahryari

Keller

Meierhofer

et al. 2023

Front. Bioeng. Biotechnol.

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“…Furthermore, free fatty acid infiltration in obesity leads to adipose tissue dysfunction. Increased levels of hepatic free fatty acids lead to increased lipid synthesis and gluconeogenesis [ 127 , 128 ]. Increased hepatic free fatty acids lead to peripheral insulin resistance, contributing to inflammation by serving as ligands for Toll-like receptor (TLR) 4 and inducing cytokine production, thereby contributing to NAFLD [ 122 , 129 ].…”

Section: Bioactive Components Of M Oleifera and Th...mentioning

confidence: 99%

Bioactive Compounds in Moringa oleifera: Mechanisms of Action, Focus on Their Anti-Inflammatory Properties

Chiș,

Noubissi,

Pop

et al. 2023

Plants

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Moringa oleifera (M. oleifera) is a tropical tree native to Pakistan, India, Bangladesh, and Afghanistan; it is cultivated for its nutritious leaves, pods, and seeds. This scientific study was conducted to outline the anti-inflammatory properties and mechanisms of action of bioactive compounds from M. oleifera. The existing research has found that the plant is used in traditional medicine due to its bioactive compounds, including phytochemicals: flavonoids and polyphenols. The compounds are thought to exert their anti-inflammatory effects due to: (1) inhibition of pro-inflammatory enzymes: quercetin and kaempferol inhibit the pro-inflammatory enzymes (cyclooxygenase and lipoxygenase); (2) regulation of cytokine production: isothiocyanates modulate signaling pathways involved in inflammation, such as the nuclear factor-kappa B (NF-kappa B) pathway; isothiocyanates inhibit the production of pro-inflammatory cytokines such as TNF-α (tumor necrosis factor α) and IL-1β (interleukin-1β); and (3) antioxidant activity: M. oleifera contains flavonoids, polyphenols, known to reduce oxidative stress and inflammation. The review includes M. oleifera’s effects on cardiovascular protection, anti-hypertensive activities, type 2 diabetes, inflammatory bowel disease, and non-alcoholic fatty liver disease (NAFLD). This research could prove valuable for exploring the pharmacological potential of M. oleifera and contributing to the prospects of developing effective medicines for the benefit of human health.

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“…Hepatic steatosis is characterized by abnormal liver lipid accumulation, which is mainly caused by impaired fatty acid metabolism, continuously circulating fatty acids from adipose tissue lipolysis, and de novo lipogenesis (DNL) [3]. Dyslipidemia is also often accompanied by liver inflammation and metabolic disorders, such as insulin resistance [7,8]. A panel of experts has suggested a new name for NAFLD, metabolic dysfunction-associated fatty liver disease (MAFLD) that is defined by the evidence of hepatic steatosis with one of the following three criteria: overweight or obesity, presence of T2DM, or evidence of metabolic dysregulation [9].…”

Section: Introductionmentioning

confidence: 99%

Molecular mechanisms of metabolic disease-associated hepatic inflammation in non-alcoholic fatty liver disease and non-alcoholic steatohepatitis

Zhang,

Sui,

Liu

et al. 2023

Explor Dig Dis

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Non-alcoholic fatty liver disease (NAFLD) is the leading chronic liver disease worldwide, with a progressive form of non-alcoholic steatohepatitis (NASH). It may progress to advanced liver diseases, including liver fibrosis, cirrhosis, and hepatocellular carcinoma. NAFLD/NASH is a comorbidity of many metabolic disorders such as obesity, insulin resistance, type 2 diabetes, cardiovascular disease, and chronic kidney disease. These metabolic diseases are often accompanied by systemic or extrahepatic inflammation, which plays an important role in the pathogenesis and treatment of NAFLD or NASH. Metabolites, such as short-chain fatty acids, impact the function, inflammation, and death of hepatocytes, the primary parenchymal cells in the liver tissue. Cholangiocytes, the epithelial cells that line the bile ducts, can differentiate into proliferative hepatocytes in chronic liver injury. In addition, hepatic non-parenchymal cells, including liver sinusoidal endothelial cells, hepatic stellate cells, and innate and adaptive immune cells, are involved in liver inflammation. Proteins such as fibroblast growth factors, acetyl-coenzyme A carboxylases, and nuclear factor erythroid 2-related factor 2 are involved in liver metabolism and inflammation, which are potential targets for NASH treatment. This review focuses on the effects of metabolic disease-induced extrahepatic inflammation, liver inflammation, and the cellular and molecular mechanisms of liver metabolism on the development and progression of NAFLD and NASH, as well as the associated treatments.

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Alterations of Central Liver Metabolism of Pediatric Patients with Non-Alcoholic Fatty Liver Disease

Cited by 6 publications

References 47 publications

On the relationship between metabolic capacities and in vivo viscoelastic properties of the liver

On the relationship between metabolic capacities and in vivo viscoelastic properties of the liver

Bioactive Compounds in Moringa oleifera: Mechanisms of Action, Focus on Their Anti-Inflammatory Properties

Molecular mechanisms of metabolic disease-associated hepatic inflammation in non-alcoholic fatty liver disease and non-alcoholic steatohepatitis

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